Chronic hypoxia impairs adrenergic responsiveness. A modulation of GS and/or Gi protein `-subunits may be associated with the downregulation of the a-adrenergic receptors previously found in chronic hypoxia. G protein gene expression and protein level and function in rat hearts exposed to a 30-day hypobaric chronic hypoxia were compared with control rat hearts. No change was observed in G`s mRNA levels in either right or left ventricles. In right ventricles, mRNA levels of G`i-2 increased by 40% (P < 0.05), but not in left ventricles. In both left and right ventricles, chronic hypoxia did not modify G`i-2 and G`s protein amounts, but significantly decreased functional activity of G`s. In conclusion, gene expression, protein levels of G`s and G`i-2, and activity of G`s do not change in parallel fashion with chronic hypoxia. In chronic hypoxic right ventricles, although the mRNA level of G`i-2 is increased, the protein level is unchanged. One potential mechanism of desensitization to catecholamines in chronic hypoxia appears to involve a decreased functional